Process for preparing phosphorothioates and phenylphosphonothioates

ABSTRACT

Mixtures of (1) a quaternary ammonium salt(s) and (2) a diazole are novel catalysts in the process of reacting an alkali metal phenate, pyridinate or pyrimidinate with an O,O-dialkyl phosphorochloridothioate or O-alkyl phenylphosphonochloridothioate to produce the corresponding title compounds. The process is conducted under alkaline conditions in a liquid reaction medium. As an example, O,O-diethyl O-(3,5,6trichloro-2-pyridyl)phosphorothioate is prepared in excellent yields and purity by reacting sodium 3,5,6-trichloro-2-pyridinate with O,O-diethyl phosphorochloridothioate in a stirred methylene chloride-water reaction medium in the presence of a catalytic amount of benzyltriethylammonium chloride and 1-methylimidazole.

United States Patent Kroposki et al.

E Nov. 4, 1975 PROCESS FOR PREPARING PHOSPHOROTHIOATES AND PHENYLPHOSPHONOTHIOATES Inventors: Lorraine M. Kroposki, Walnut Creek, Calif.; Masao Yoshimine, Midland, Mich.; Harold H. Freedman, Newton Center, Mass.

The Dow Chemical Company, Midland, Mich.

Filed: Apr. 24, 1973 Appl. No.: 354,040

Related US. Application Data Continuation-in-part of Ser. No. 229,171, Feb. 24, 1972, abandoned.

Assignee:

US. Cl. 260/294.8 K; 260/250 R; 260/251 P; 260/297 P; 260/465 F; 260/465 G; 260/465 Int. C1. C07D 213/83 Field of Search 260/294.8 K, 297 P, 294.9

References Cited UNlTED STATES PATENTS 4/1966 Rigterink 260/294.8 K

FOREIGN PATENTS OR APPLlCATlONS 1,227,144 4/1971 United Kingdom 260/454 Primary E.raminer-Alan L. Rotman Attorney, Agent, or FirmL. Wayne White [57] ABSTRACT 19 Claims, No Drawings PROCESS FOR PREPARING PHOSPHOROTHIOATES AND PI-IENYLPIIOSPHONOTI-IIOATES CROSS-REFERENCE TO RELATED APPLICATION This is a continuation-in-part of our US. patent application Ser. No. 229,171, filed Feb. 24, 1972, now abandoned.

BACKGROUND OF THE INVENTION The O-pyridyl phosphates and phosphorothioates were described by Rigterink in US. Pat. No. 3,244,586. Such compounds are particularly useful as insecticides and biocides. They are represented by Formula I wherein R represents halopyridyl, Z represents oxygen or sulfur and each R independently represents lower alkyloxy, amino or lower alkylamino. Rigterink disclosed several methods for preparing the compounds but his preferred method comprised reacting a phosphorochloridate or phosphorochloridothioate of Formula (II) Cl-P-R' with an alkali metal or tertiary amine salt of a halopyridinol having the formula R-O-alkali metal or R-OI-l'tertiary amine. The disclosed methods were carried out in an inert organic liquid under anhydrous conditions. In each of the disclosed processes an alkali metal chloride or the tertiary amine hydrochloride salt is produced as a reaction by-product which is removed by filtration. The disclosure of US. Pat. No. 3,244,586 is incorporated herein by reference.

Other phosphorothioates and phenylphosphonothioates have been similarly prepared and used. See, for example, the articles by 0. Johnson in Chemical Week, pages 18-46 (26 July 1972) and by E. E. Kenaga and W. E. Allison in the Bulletin of the Entomological Society of America, Vol. 15, No. 2, pages 85-148 (June, 1969) which list many commercially available phosphorothioates and phenylphosphonothioates and which include US. patents pertaining to such compounds.

The phosphorothioates and phenylphosphonothioates referred to above and herein prepared correspond to the formula R and R are each independently lower alkyl; and R is wherein:

n is 0, l, 2 or 3; and X is nitro, cyano, halo (fluoro, chloro, bromo and iodo, inclusive), lower alkyl, lower alkoxy, lower alkylthio or lower alkylsulfinyl, with the proviso that R does not bear more than one nitro group, lower alkylthio group or lower alkylsulfinyl group. By lower alkyl is meant in all instances alkyl of 1 to 4 carbon atoms (i.e. methyl, ethyl, propyl and butyl).

SUMMARY OF THE INVENTION We have discovered that mixtures of (1) a quaternary ammonium salt(s) and (2) a diazole are novel catalysts in the process comprising reacting by contacting (a) an alkali metal phenate, pyridinate and pyrimidinate with (b) an 0,0-dialkyl phosphorochloridothioate or 0,0-dialkyl phenylphosphonochloridothioate to produce the corresponding 0,0-dia1kyl phosphorothioate and phenylphosphonothioa'tes. Our novel two-component catalyst represents a substantial process improvement over the prior art in that the reaction rate is higher and the desired products are obtained in extremely high yields and purity.

THE QUATERNARY AMMONIUM SALTS Essentially any compound from the known class of quaternary ammonium compounds can be used in the instant invention. Suitable quaternary ammonium salts have a minimum solubility of at least about 1 weight percent in the liquid reaction medium at 25C., and in the case of a twophase reaction medium described below, suitable salts have a minimum solubility of at least about 1 weight percent in both the organic phase and the aqueous phase at 25C. The ammonium salts can be represented by the formula R',R' R' R' N A (VI), wherein R R are hydrocarbyl groups (e.g. alkyl, aryl, alkaryl, aralkyl, cycloalkyl, etc.) and R can join with R, to form a 5- or 6-membered heterocyclic compound having at least one quaternized nitrogen atom in the ring and may also contain one atom of nitrogen, oxygen or sulfur within the ring. Typically, R R are hydrocarbyl groups of from 1 to about 12 carbon atoms. A in V1 is a neutralizing anion and may be varied to convenience. Chloride and bromide are the preferred anions, but other representative anions include fluoride, iodide, tosylate, acetate, bisulfate, etc. The following compounds are illustrative: tetraalkyl ammonium salts, such as tetramethy1-., tetraethyl-, tetrabutyl-, tetrahexyl-, methyltriethyl-, and trioctylmethyland tridecylmethyl-ammonium chlorides, bromides, iodides, bisulfates, tosylates, etc.; aralkylammonium salts, such as tetrabenzylammonium chloride, benzyltrirnethyl-, benzyltriethylbenzyltributy1-, and phenethyltrimethylammonium chlorides, bromides, iodides, etc.; arylammonium salts, such as triphenylmethylam- I monium fluoride, chloride or bromide, N,N,N-trimethylanilinium chloride, N,N,N-triethylanilinium bromide, N,N-diethyl-N-ethylanilinium bisulfate, trimethylnaphthylammonium chloride, p-methylphenyltrimethylammonium chloride or tosylate, etc.; 5- and 6-membered heterocyclic compounds containing at least one quaternized nitrogen atom in the ring, such as N,N,N',N'-tetramethylpiperaziniumdichloride, N- methylpyridiniumchloride, N-methylpyridinium chloride, N-hexylpyridinium iodide, 4-pyridyltrimethylammonium iodide, l-methyl-l-azoniabicyclo[2.2.l]heptane bromide, N,N-dibutylmorpholinium chloride, N- ethylthiazolium chloride, N-butylpyrrolium chloride, etc., and other like compounds.

THE DIAZOLES Diazoles form a known class of compounds. Diazoles suitable for use in the instant process are imidazoles and pyrazoles of the formulas F N [N -N and R -N (VI) (VII) respectively. In VI and VII, R is hydrogen or lower alkyl of from 1 to 6 carbon atoms and is preferably hydrogen, methyl or ethyl and is most preferably methyl. Further, the imidazoles are presently preferred over the pyrazoles. Examples of suitable such diazol es include imidazole, l-methylimidazole, l-ethylimidazole, lpropylimidazole, l-hexylimidazole, pyrazole, l-methylpyrazole, l-ethylpyrazole, l-butylpyrazole, l-amylpyrazole and l -hexylpyrazole, and the like.

THE NOVEL CATALYSTS Any combination of quaternary ammonium compound and diazole within the above definitions for such compounds can be used as the catalyst for the above mentioned reaction. However, the preferred catalyst system is a mixture of benzyltrimethylammonium chloride (or bromide) or benzyltriethylammonium chloride (or bromide) and l-methylimidazole and the most preferred catalyst system is a mixture of benzyltriethylammonium chloride and l-methylimidazole.

The mole ratio of l to (2) can vary from about 1:20 to 20:1, but a mole ratio of about 1:2 to 2:1 is preferred in most instances.

The mixtures of( 1 and (2) are used in the process in small but catalytic amounts. For example, amounts from about 0.25 to about 20 mole'percent, based on the reactants, are suitable but amounts of from about 0.5 to about 2 mole percent are generally preferred.

PROCESS PARAMETERS The reaction proceeds at a satisfactory rate at temperatures,of from about up to about 100C. with a preferred rate being obtained at temperatures of about 40-60C. The reaction pressure is not critical and generally atmospheric or superatmospheric pressures are used 'as a matter of convenience. Under the above conditions, reaction times of up to 8 hours are common althoughreaction times of from 0.25 to hours are generally sufficient for the reaction to be substantially complete.

The process is typically conducted in a liquid reaction medium as a convenient means of controlling the reaction temperature. The solvent may be an inert organic liquid such as methylene chloride (CH CI chloroform, carbon tetrachloride, benzene, toluene, cyclohexane, and other like chlorinated hydrocarbon solvents and hydrocarbon solvents. Alternatively, the process can be conducted in a two-phase solvent system comprising an inert, water-immiscible,organic liquid and water. The two-phase system is currently preferred because the by-product chloride is washed free from the reaction and is retained in the aqueous phase while the product is retained in the organic phase. A liquid mixture of methylene chloride and water represents the most preferred solvent mixture. The discovery that the process could be conducted in the presence of water without deleteriously affecting the product yield, etc., was most surprising since the phosphorochloridates and phosphorochloridothioates are known to decompose in water. Furthermore, since the pyridinates are water-soluble and the phosphorochloridates and phosphorochloridothioates are essentially water-insoluble, the use of a two-phase solvent system would have been expected to slow the reaction since contact between the two reactants would be lessened; this effect was not observed.

The process is conducted under neutral or alkaline conditions. Generally the pH of the water phase (when present) is in the range of from about 7 to about 13. Such conditions can be easily achieved by conventional methods, e.g. by conducting the process. in the presence of caustic, or other base or by use of an appropriate buffer system.

Agitation (e.g., stirring, swirling, etc.) of the reaction mixture is advantageous, particularly when the process is conducted in the two-phase liquid reaction medium.

THE REACTANTS The alkali metal phenates, pyridinates and pyrimidinates are known classes of compounds corresponding to the formulas (VIII) 6 (1x wherein R has the above meaning and M is an alkali metal (Li, Na, K, etc.) but is preferably sodium or potassium and is most preferably sodium.

- The 0,0-dialkyl phosphorochloridothioates and 0- alkyl phenylphosphonochloridothioates are likewise well known classes of compounds which correspond to the formulas R -o-t -cl and c H E -Cl R -O R -O wherein R and R are each independently lower alkyl but are preferably methyl or ethyl.

Various phosphorothioates and phenylphosphonothioates can obviously be prepared by using various combinations of the above reactants. Representative and illustrative lists of suitable reactants and combinations thereof are shown in Tables 1 and 2 below:

Table l s s R -O-1PCl R-o l a R-O-P-O-R I I R -O O-R c1 N 1 CH CH Na 2 C2H5 15 1 Na F 3 c 11 c 11 Na Cl 4 CH3 CH3 QCl Na c1 c1 5 c 11 C2115 @11 K c1 6 CH3 CH3 G-I Na c1 7 CH3 c11 @110 Na 8 c 11 c 11 N02 Na 9 CH3 CH3 @510 K 0 10 CH3 CH3 N K 11 CH3 CH3 @s-cr1 Na 0 12 CH CH "-cH Na 13 c H c 11 sea Na N 3, 2 ,'l\ K 14 c 11 CZHS N 1 Table 1 (continued) 5 s R2OPC 1 RO% R-O-P-O-R2 R O o-R 15 c H c H bi Na l6 CH3 CH3 @421 K Table 2:

R e m C1 17 C11 Q Na l8 c H @NOZ K I 19 c 11 N Na The compounds of Formula V are prepared in like manner.

The following examples further illustrate the invention.

EXAMPLE 1 Preparation of 0,0-Dimethyl-O-3 ,5 ,6-Trichloro-2-Pyridylphosphorothioate To a three-necked flask, equipped with a stirrer, condenser and a dropping funnel, was added 30 ml. methylene chloride, 74 ml. of water, 3.3 gm. of sodium chloride, 0.38 gm. of sodium hyroxide, 0.7 gm. of boric acid, 0.13 gm. (0.56 mmoles) of benzyltriethylammonium chloride and 0.05 gm. (0.56 mmoles) of lmethylimidazole and 12.5 gm. (56 mmoles) sodium 3,5,6-trichloro-2-pyridinate (NaTCP). The stirred mixcent).

In like manner the following runs were conducted:

Table 2A 0.0-Dimethyl--3.5,6-Trichloro-2-Pyridylphosphorothioate 8 acid, 0.14 gm. (0.6 mmole) of benzyltriethylammonium chloride, 0.04 gm. (0.45 mmole) of 1- methylimidazole and 13.2 gm. (60 mmoles) NaTCP. The stirred mixture was heated to C. and 11.3 gms. mmole) of 0,0-diethylphosphorochloridothioate (DEPCT) was added over a 1 minute period and brought the reaction mixture to reflux (42C.). The stirred reaction mixture was refluxed for 3.9 hours. The CH Cl layer was separated and washed with ml. of water. Then the CH Cl was removed on a rotary evaporator. The product was cooled in an ice water bath to Benzyltriethylammonium l-Methylimidazole Time, Yield,

Chloride, Mole Mole, Hrs. give 19.41 gm. of white crystals (92.43 percent yield of 1 l L6 product having a purity of 99.5 percent). 0.75 0.75 3.8 94.9 In like manner the following runs were conducted:

Table 3 0.0-Diethyl-O-3,5,6-Trichloro-2-Pyridylphosphorothioate Benzyltriethylammonium l-Methylimidazole,

Chloride, Mole Mole Time, Hrs. Yield, Purity,

lmidazole, Mole 5 5 7.1 94.6

Pyrazole, Mole 5 5 28 88.5

Isolated yield 0.50 0.50 4.5 94.6 EXAMPLES 3 0.75 0.50 3.1 91.7 l 23 The following experiments were conducted uslng substantially the same procedure. In each instance the Isolated yield catalyst used was a mixture of benzyltriethylammonium PLE 2 35 chloride and l-methylimidazole. The catalyst level for Preparation of 0,0-Diethyl-O-3 ,5 ,6-Trichloro-Z-Pyridylphorothioate To a three-necked flask, equipped with a stirrer, condenser and a dropping funnel, was added 30 ml. methy- 0 lene chloride, 74 ml. of water, 3.5 gm. of sodium chloride, 0.43 gm. of sodium hydroxide, 0.78 gm. of boric Table 4 Reaction Conversion Yield' Product 133: Reactants Product Time (11175.) (Z) Descrlpt 1.011

3 DMPCT Na 0@-SCH (cH 0)- P(s)-o-@scr1 2.5 100 95.1. Red 0'11 c11 CH3 c1 c1 4 C6H P(S) c1+ 9 0--Br)C l-l -P(S)0@Br 2.5 78.1 95.4 White Solid I I 011 -0 Cl c11 0 01 s DMPCI N O'QNO (011 09- )-o (kN0 3 100 ca.l00 Brown liquid N W N t 0 DEPCl N. (c H -0+ P(s)- O 7 Measured 83 N F N F N N 7 DEPCT Ne1 0- O ;(C H 0- P(S)0-(LS b Measflred 86 c c] s DMPCT N5 @CI cH o- P(s)-0- Q -Cl 1 100 92 --PcrccnL yield is based on material converted.

examples 3-7 was 0.75 mole percent for each catalyst component based on combined starting materials, and was 1.0 mole percent for each catalyst component in example 8. Further, boric acid was included in examples 3-5 (as per examples 1 and 2) but boric acid was not included in examples 68. The experimental results are summarized in Table 4.

Based on conversion of phcnatc, pyridinate o1: pyrimidinate reactant (100% assumed for Ex. 6 and 7).

Those skilled in the art will recognize that the above examples are merely illustrative and that other novel catalyst mixtures could be used as described above. Additionally, they will recognize that compounds could be similarly prepared by using various combinations of reactants as described above.

We claim:

1. In the process of preparing a compound corresponding to the formula wherein:

R and R are each independently lower alkyl; and R (j (3 Q) Q 9 GB 9 G) a-o n or M OC H SC H O M with (b) a compound corresponding to the formula R -O?-Cl or C H I Cl R O R O wherein M is an alkali metal and R, R and R have the aforesaid meaning;

the improvement consisting of conducting the process in the presence ofa small but catalytic amount of 1) a quaternary ammonium salt having a minimum solubility of at least 1 weight percent in the liquid reaction medium at 25C. and (2) a diazole corresponding to the formula wherein R is hydrogen or alkyl of l to 6 carbon atoms. 2. The process defined in claim 1 wherein (l) is an ammonium salt of the formula 1 l R R R R N A wherein R --R are each independently hydrocarbyl groups of from 1 to about 12 carbon atoms, or R is joined with R' to form a 5- or 6-membered heterocy- 10 clic having at least one qua'ternized nitrogen atom within the ring and may additionally contain one nonadjacent atom of nitrogen, oxygen or sulfur within the ring; and A is an neutralizing anion.

3. The process defined in claim 2 wherein (1) is benzyltrimethylammonium chloride or bromide, or benzyltriethylammonium chloride or bromide.

4. The process defined in claim 3 wherein (1) is benzyltriethylammonium chloride.

5. The process defined in claim 1 wherein (2) is wherein R has the aforesaid meaning.

6. The process defined in claim 1 wherein R is hydrogen, methyl or ethyl.

7. The process defined in claim 6 wherein R is methyl.

8. The process defined in claim 1 wherein the mole ratio of l) to (2) is from about 1:20 to about 20:1.

9. The process defined in claim 8 wherein said ratio is from about 1:2 to about 2:1.

10. The process defined in claim 1 wherein the combined amount of (l) and (2) is from about 0.25 to about 20 mole percent, based on the combined moles of (a) and (b).

l l. The process defined in claim 10 wherein the combined amount of 1 and (2) is from about 0.5 to about 2 mole percent.

12. The process defined in claim 1 wherein said process is conducted in an agitated two-phase solvent system consisting of an inert water-immiscible organic liquid and water.

13. The process defined in claim 1 wherein R and R are methyl or ethyl.

14. The process defined in claim 13 wherein R is wherein R is hydrogen methyl or ethyl.

17. The process defined in claim 16 wherein said process is conducted in an agitated twophase solvent system consisting of an inert water-immiscible organic liquid and water.

18. The process defined in claim 17 wherein (a) is sodium O-3,5,6-trichloro-2-pyridinate and (b) is 0,0- dimethyl or 0,0-diethyl phosphorochloridothioate; (l is benzyltriethylammonium chloride; (2) is lmethylimidazole; said two-phase solvent system is a mixture of methylene chloride and water; and the reaction temperature is from about 40 to about C.

19. The process defined in claim 18 wherein (b) is 0,0-diethyl phosphorochloridothioate.

UNITED STATES PATENT AND TRADEMARK OFFICE CERTIFICATE OF CORRECTION PATENT N0. 3,917,621

DATED November 4, 1975 INVENTOR(S) I Lorraine M. Kroposki, Masao Yoshimine, and Harold H. Freedman It is certified that error appears in the above identified patent and that said Letters Patent are hereby corrected as shown below:

Column 6, line 54:

Column 7,

Column 9,

Column 10,

Column 10,

[SEAL] "hyroxide" should read -hydroxide.

line 37: "2-Pyridylphorothioate" should read 2- Pyridylphosphorothioate-.

N line 25: @AX) should read line 4, Claim 2, line 10: "an" should read a.

should be line 43, Claim 14, line 2:

' deleted.

A ttes t:

RUTH C. MASON Arresting Officer C. MARSHALL DANN Commissioner oflarents and Trademarks 

1. IN THE PROCESS OF PREPARING A COMPOUND CORRESPONDING TO THE FORMULA
 2. The process defined in claim 1 wherein (1) is an ammonium salt of the formula R''1R''2R''3''R''4N A wherein R''1-R''4 are each independently hydrocarbyl groups of from 1 to about 12 carbon atoms, or R''1 is joined with R''2 to form a 5- or 6-membered heterocyclic having at least one quaternized nitrogen atom within the ring and may additionally contain one non-adjacent atom of nitrogen, oxygen or sulfur within the ring; and A is an neutralizing anion.
 3. The process defined in claim 2 wherein (1) is benzyltrimethylammonium chloride or bromide, or benzyltriethylammonium chloride or bromide.
 4. The process defined in claim 3 wherein (1) is benzyltriethylammonium chloride.
 5. The process defined in claim 1 wherein (2) is
 6. The process defined in claim 1 wherein R3 is hydrogen, methyl or ethyl.
 7. The process defined in claim 6 wherein R3 is methyl.
 8. The process defined in claim 1 wherein the mole ratio of (1) to (2) is from about 1:20 to about 20:1.
 9. The process defined in claim 8 wherein said ratio is from about 1:2 to about 2:1.
 10. The process defined in claim 1 wherein the combined amount of (1) and (2) is from about 0.25 to about 20 mole percent, based on the combined moles of (a) and (b).
 11. The process defined in claim 10 wherein the combined amount of (1) and (2) is from about 0.5 to about 2 mole percent.
 12. The process defined in claim 1 wherein said process is conducted in an agitated two-phase solvent system consisting of an inert water-immiscible organic liquid And water.
 13. The process defined in claim 1 wherein R1 and R2 are methyl or ethyl.
 14. The process defined in claim 13 wherein R is
 15. The process defined by claim 14 wherein (1) is benzyltrimethylammonium chloride or bromide or benzyltriethylammonium chloride or bromide.
 16. The process defined in claim 15 wherein (2) is
 17. The process defined in claim 16 wherein said process is conducted in an agitated two-phase solvent system consisting of an inert water-immiscible organic liquid and water.
 18. The process defined in claim 17 wherein (a) is sodium O-3,5, 6-trichloro-2-pyridinate and (b) is O,O-dimethyl or O,O-diethyl phosphorochloridothioate; (1) is benzyltriethylammonium chloride; (2) is 1-methylimidazole; said two-phase solvent system is a mixture of methylene chloride and water; and the reaction temperature is from about 40* to about 60*C.
 19. The process defined in claim 18 wherein (b) is O,O-diethyl phosphorochloridothioate. 